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Aaron Ciechanover, MD, DSc

Aaron Ciechanover, MD, DSc

Grant Status

Technion, Israel Institute of Technology

Grant Type
Research Professorship Grant

Project Title
Unraveling the Tumor-Suppressing Mechanisms Involved in Ubiquitin-Mediated Activation of NF-kappaB

Tumor Types

Research Topics
Inflammation and Cancer, Oncogenesis, Ubiquitin System

Named Grant

The Mark z”l & Zita z”l Bernstein Research Professorship Grant

About the Investigator:

Born in Haifa, Israel, Prof. Ciechanover received his MD degree from the Hebrew University of Jerusalem, then completed his national service as a military physician, before continuing his studies to obtain a doctorate in biological sciences (DSc) from the Faculty of Medicine at the Technion. There, as a graduate student with Prof. Avram Hershko, they discovered that attachment of ubiquitin to a target protein signals it for degradation. As a post-doctoral fellow at MIT, he continued his studies on the ubiquitin system and made additional important discoveries. He is currently a Distinguished Research Professor in the Faculty of Medicine at the Technion. Among the numerous honors that Ciechanover has received are the 2000 Albert Lasker Prize for Basic Medical Research, the 2002 EMET Prize in Life Sciences, the 2003 Israel Prize in Biology, and the 2004 Nobel Prize in Chemistry (shared with Profs. Hershko and Rose). Over the years, it has become clear that the ubiquitin system plays major roles in numerous cellular processes, and abnormalities in the system underlie the causes of many diseases, such as cancers and neurodegenerative disorders. Consequently, the ubiquitin system has become an important platform for drug development.

About the Research:

In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating genetic activity. The NF-kappaB protein is a key transcriptional regulator involved in inflammation, cell proliferation, survival, and malignant transformation. It is involved in many tumor types and plays important roles in both initiating the malignant process and in promoting tumor growth once they are formed. It acts both directly and indirectly via transcriptional activation of survival genes in the tumor cells, and inflammation-promoting genes in the tumor microenvironment.

Several key steps in the activation of NF-kappaB are mediated by the ubiquitin-proteasome system that was discovered by Prof. Ciechanover and his colleagues. Based on this discovery, several successful drugs have already been developed by pharmaceutical companies, mostly against multiple myeloma, and many more are in the pipeline. The goal of his current research project is to unravel the mechanisms by which NF-kappaB — the Mr. Hyde of inflammation and carcinogenesis — becomes Dr. Jekyll — a strong tumor suppressor. By employing a combined approach of molecular and cellular biological techniques, as well as genetically-manipulated animals, along with the examination of human tumor tissues, Prof. Ciechanover aims to shed light on this mechanism of tumor suppression, with the hope that it will be possible to harness it in the future for the development of novel therapeutics.


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